MT-1207
Based on 1 Customer Validation
MT-1207 is an orally active, selective adrenergic α1 and 5-HT2A receptor antagonist. The IC50 values of MT-1207 for α1A, α1B, α1D, and 5-HT2A are <0.1 nM, 0.15 nM, 1.40 nM, and 0.27 nM, respectively. MT-1207 induces vasodilation, improves baroreflex sensitivity, and reduces heart rate in isolated hearts. MT-1207 lowers blood pressure, protects the heart, brain, and kidneys, improves cognition, delays stroke, reduces mortality, and lowers uric acid without impairing renal function in SHR/2K1C/2K2C models. MT-1207 exhibits high plasma protein binding, resistance to plasma esterases, and NADPH-dependent hepatic metabolism. MT-1207 can be used for research related to hypertension.
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity : 99.96%
- CAS No.: 1610794-70-1
- 화학식: C21H25ClN6S
- 분자량:428.98
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보관:
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
5-HT2A Receptor |
α1A-adrenergic receptor 0.1 nM (IC50) |
α1B-adrenergic receptor 0.15 nM (IC50) |
α1B-adrenergic receptor 1.40 nM (Ki) |
α1D-adrenergic receptor 0.086 nM (IC50) |
α1D-adrenergic receptor 0.69 nM (Ki) |
5-HT2A Receptor 0.27 nM (IC50) |
5-HT2A Receptor 0.079 nM (Ki) |
In Vitro
MT-1207 binds stably to α1A, α1B, α1D, 5-HT2A, 5-HT2B, and 5-HT2C receptors through hydrogen bonds, hydrophobic interactions, and van der Waals forces[1].
MT-1207 (0.1 nM-1 μM) effectively inhibits adrenergic α1A, α1B, α1D and 5-HT2A receptors with high binding affinity[3].
MT-1207 (1-100 nM; 60 min) is a potent multi-target antagonist of α1-adrenoceptor subtypes and 5-HT2A receptors in CHO cell membranes[2].
MT-1207 (10-1000 ng/mL; 30 min) exhibits extremely high plasma protein binding rates in Sprague-Dawley rat, beagle dog, cynomolgus monkey, and human plasma[2].
MT-1207 (1 μg/mL; 0-120 min) exhibits strong plasma stability in human, Sprague-Dawley rat, Beagle dog, and cynomolgus monkey plasma, and is resistant to enzymatic hydrolysis by plasma esterases[2].
MT-1207 (10 μM; 0-120 min) undergoes rapid NADPH-dependent metabolism in rat, beagle dog, cynomolgus monkey, and human liver microsomes[2].
MT-1207 (0.2 ng/mL-2000 μg/mL; 20 min) does not significantly inhibit CYP3A4, CYP2C9, CYP1A2, and CYP2C19 in human liver microsomes, but exhibits a certain degree of CYP2D6 inhibition at higher concentrations[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MT-1207 (10-20 mg/kg/d; p.o.; daily; 3 days to 9 weeks) reverses renal dysfunction and reduces uric acid levels in 2K2C rats[1].
MT-1207 (10 mg/kg/d; p.o.; daily; 2 weeks) exerts uric acid-lowering effects in a hyperuricemia model[1].
MT-1207 (10-20 mg/kg/d; p.o.; 9 weeks) ameliorates cognitive dysfunction in 2K2C rats[1].
MT-1207 (10-20 mg/kg/d; p.o.; 9 weeks) exhibits cardiovascular and renal protective effects in 2K2C rats[1].
MT-1207 (10 mg/kg/d; p.o.; lifelong) reduces mortality and extends lifespan in 2K2C rats[1].
MT-1207 (1 mg/kg; i.v.) blocks α1 and 5-HT2 receptors in vivo[1].
MT-1207 (10 mg/kg/day; p.o.; 4 months) stably lowers blood pressure, improves baroreflex sensitivity, and provides renal and cardiovascular organ protection[3].
MT-1207 (10 mg/kg/day; p.o.; approximately 8 months) stably lowers blood pressure and improves survival in stroke-prone SHR by delaying the onset of stroke and death[3].
MT-1207 (10 mg/kg; p.o.; daily; 9 weeks) effectively lowers blood pressure without impairing renal function in the 2K2C renovascular hypertensive rat model[2].
MT-1207 (2.5-10 mg/kg; p.o.; single dose) effectively lowers blood pressure in rats without causing the side effect of orthostatic hypotension[2].
MT-1207 (250-1000 mg/kg; p.o.; single dose) is well tolerated in SD rats, with a maximum tolerated dose exceeding 1000 mg/kg[2].
MT-1207 (10-100 mg/kg; p.o.; once daily; 13 weeks) is tolerated at all dose levels over 13 consecutive weeks, with a no-observed-adverse-effect level (NOAEL) of 100 mg/kg[2].
MT-1207 (1.25-20 mg/kg; p.o.; single dose) produces a rapid, dose-dependent antihypertensive effect without inducing reflex tachycardia[3].
MT-1207 (0.25-6 mg/kg; p.o.; single dose) dose-dependently lowers systolic blood pressure in 2K1C dogs, with effects maintained for over 12 h and without causing reflex tachycardia[3].
MT-1207 (5 mg/kg/day; p.o.; once daily; for 7 consecutive days) significantly lowers systolic blood pressure and slightly slows heart rate without affecting ECG[3].
MT-1207 (2 mg/kg/day; p.o.; once daily; for 7 consecutive days) significantly lowers systolic blood pressure and slightly slows heart rate, accompanied by minor ECG changes that recover after drug withdrawal[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague Dawley (Male; 160-180 g)[1]
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Dosage:10 mg/kg/d
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Administration:p.o.; daily; 4 and 9 weeks
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Result:Decreased systolic BP to 219 mmHg at the 4th week and 211 mmHg at the 9th week.
Showed a similar reducing effect on diastolic BP.
Had no significant effect on HR.
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Animal Model:Sprague Dawley (Male; 160-180 g)[1]
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Dosage:10 mg/kg/d (acute); 10 and 20 mg/kg/d (long-term)
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Administration:p.o. (gavage); once a day; 3 days (acute); p.o. (drug-containing diet); 9 weeks (long-term)
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Result:Acute administration of MT (10 mg/kg/d) for 3 days decreased the serum uric acid level compared with the 2K2C model group, and it maintained serum creatinine, urea, and K+ concentrations at the same levels as sham-operated rats.
In the long-term experiment, MT did not deteriorate renal function in either group, but showed a significant uric acid-lowering effect compared with the 2K2C model group, and maintained serum K+ levels as sham-operated rats.
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Animal Model:Sprague Dawley (Male)[1]
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Dosage:10 mg/kg/d
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Administration:p.o. (gavage); once a day; 2 weeks
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Result:Significantly reduced serum uric acid levels after 1 and 2 weeks of administration.
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Animal Model:Sprague Dawley (Male; 160-180 g)[1]
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Dosage:10 and 20 mg/kg/d
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Administration:p.o. (drug-containing diet); 9 weeks
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Result:Both MT (10 and 20 mg/kg/d) long-term treatment groups were able to significantly reduce the swimming distance and latency, indicating an effect of improving the learning memory dysfunction in rats.
Two doses of MT showed different degrees of improvement in frequency of crossing the platform and the residence time in the target quadrant.
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Animal Model:Sprague Dawley (Male; 160-180 g)[1]
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Dosage:10 and 20 mg/kg/d
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Administration:p.o. (test-article-containing diet); 9 weeks
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Result:Both MT (10 and 20 mg/kg/d) significantly improved cardiac and aortic hypertrophy.
The renal cortex to medulla thickness ratio in kidneys that did not undergo atrophy showed a slight improvement in the MT group.
The smaller kidney/larger kidney weight ratio in MT 10 mg/kg/d and 20 mg/kg/d groups showed different degrees of atrophy, and after MT treatment, the degree of atrophy was somewhat alleviated.
The incidence of atrophy was 60% in the MT 10 mg/kg/d group and 45.5% in the MT 20 mg/kg/d group.
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Animal Model:Sprague Dawley (Male; 160-180 g)[1]
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Dosage:10 mg/kg/d
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Administration:p.o. (drug-containing diet); lifelong
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Result:Significantly prolonged the survival time of the rats, up to nearly 5 months.
Alleviated the continuous death of rats in the early stage and effectively reduced the death of animals.
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Animal Model:Sprague Dawley (Male; 160-180 g)[1]
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Dosage:1 mg/kg
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Administration:i.v.; single administration
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Result:In rats with vehicle pre-treatment, phenylephrine induced a BP increase of about 90 mmHg, but this phenomenon totally disappeared in rats with MT pre-treatment.
Likewise, MT had an inhibitory effect on 2,5-dimethoxy-4-iodoamphetamine-induced BP increase.
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Animal Model:Sprague-Dawley (SD) (Male, 160-180 g, 2K2C renovascular hypertensive model)[2]
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Dosage:10 mg/kg
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Administration:p.o.; daily; 9 weeks
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Result:Achieved a comparable antihypertensive effect to losartan (20 mg/kg), with systolic blood pressure (SBP) readings of 169 mmHg compared to approximately 202 mmHg in the 2K2C model rats.
Showed a tendency to decrease diastolic blood pressure (DBP) and did not elevate heart rate, instead causing a slight reduction.
Exhibited a minimal impact on urea, creatinine, and K+ levels, demonstrating excellent antihypertensive effects without damaging renal function in 2K2C rats.
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Animal Model:Sprague-Dawley (SD) (Male)[2]
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Dosage:2.5, 5 and 10 mg/kg
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Administration:p.o.; single dose
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Result:Effectively lowered blood pressure after 30 min at 2.5, 5, and 10 mg/kg doses.
Displayed a consistent trend in blood pressure alteration when rats changed posture, with the maximum SBP reduction occurring at 5 s, ranging from 7 to 10 mmHg.
Varying degrees of SBP recovery were observed at 10 s.
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Animal Model:Sprague-Dawley (SD)[2]
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Dosage:250-1000 mg/kg
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Administration:p.o.; single dose
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Result:No instances of unscheduled fatalities were recorded.
Rats in all groups displayed no discernible drug-related alterations in body weight or morphology.
Single oral administration at doses of 250, 500, and 1000 mg/kg in SD rats was well-tolerated, with the maximum tolerated dose (MTD) exceeding 1000 mg/kg.
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Animal Model:Sprague-Dawley (SD)[2]
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Dosage:10, 30 and 100 mg/kg
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Administration:p.o.; once daily; 13 weeks
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Result:There were no unplanned mortalities in any of the groups.
No notable drug-related changes were revealed in morphological observations or post-mortem histopathological examinations.
In the 10 mg/kg group, rats did not exhibit any significant anomalies in body weight.
In the 30 mg/kg group, male rats showed a decrease in body weight on Day 11, with a weight reduction of approximately 3.3−7.2% during the dosing period, which gradually returned to normal post-cessation.
In the 100 mg/kg group, both male and female rats displayed decreased body weights on Day 4, with a weight decrease of approximately 5.4−14.7% in male rats and 3.3−6.8% in female rats, which also gradually returned to baseline levels after drug discontinuation.
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Animal Model:Spontaneously hypertensive rats (SHR) (male, 250 ± 20 g)[3]
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Dosage:1.25, 2.5, 5, 10, 15, or 20 mg/kg
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Administration:i.g.; single dose
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Result:Decreased systolic blood pressure (BP) in all dose groups 15 min after administration.
Achieved maximal systolic BP decrease of 17 mmHg in the 1.25 mg/kg group and 21 mmHg in the 2.5 mg/kg group.
Achieved maximal systolic BP decrease of 41 mmHg in the 10 mg/kg group.
Demonstrated an obvious dose-effect relationship at 2.5, 5, and 10 mg/kg.
Decreased systolic BP by 12 mmHg at 2.5 min and 20 mmHg at 5 min after administration of 5 mg/kg.
Decreased BP significantly within 8-10 h after administration in 2.5, 5, and 10 mg/kg groups.
Did not increase heart rate but slightly decreased heart rate during BP reduction.
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Animal Model:Beagle dogs (male and female, 8-10 kg)[3]
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Dosage:0.25, 0.5, 1, 1.5, 2, 4, or 6 mg/kg
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Administration:p.o. (gavage); single dose
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Result:Dose-dependently lowered systolic BP with a maximal reduction of 55 mmHg.
Decreased systolic BP by 14 mmHg at 5 min and by more than 20 mmHg at 10 min after administration of 2 mg/kg.
Showed a significant dose-effect relationship with the decrease in systolic and diastolic BP.
Maintained the decrease in systolic BP for more than 12 h.
Did not induce a reflex increase in heart rate but decreased heart rate.
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Animal Model:Spontaneously hypertensive rats (SHR) (male, 250 ± 20 g)[3]
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Dosage:5 mg/kg/day
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Administration:p.o. (gavage); once daily; 7 consecutive days
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Result:Decreased average systolic BP from 175 ± 0.99 mmHg to 140 ± 2.43 mmHg.
Slightly slowed heart rate from 346 ± 21.88 bpm to 326 ± 16.39 bpm.
Had no significant effect on the ECG.
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Animal Model:Beagle dogs (male and female, 8-10 kg)[3]
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Dosage:2 mg/kg/day
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Administration:p.o. (gavage); once daily; 7 consecutive days
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Result:Decreased average systolic BP from 173 ± 1.45 mmHg to 139 ± 1.38 mmHg.
Slightly slowed heart rate from 150 ± 3.66 bpm to 138 ± 4.75 bpm.
Prolonged the QT interval duration and QRS duration by 0.01 s and the T wave duration by 0.02 s on the 7th day.
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Animal Model:Spontaneously hypertensive rats (SHR) (male 350 ± 20 g and female 200 ± 20 g)[3]
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Dosage:10 mg/kg/day
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Administration:p.o. (mixed in rat chow); 4 months
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Result:Decreased systolic BP by more than 20 mmHg 1 week after treatment and remained stable during 4 months.
Improved baroreflex sensitivity (BRS) to 0.53 ± 0.03 ms/mmHg compared with the vehicle control group (0.27 ± 0.01 ms/mmHg).
Significantly decreased glomerular sclerosis scores.
Improved pathological changes in the heart, brain and aorta.
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Animal Model:Stroke-prone spontaneously hypertensive rats (SHR-SP) (male, 350 ± 20 g)[3]
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Dosage:10 mg/kg/day
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Administration:p.o. (mixed in rat chow); approximately 8 months
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Result:Decreased systolic BP by more than 20 mmHg and remained stable over 4 months.
Maintained stable heart rate with an average of 410 beats/min.
Improved the survival rate by delaying stroke occurrence and death.
Chemical Information
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CAS No. 1610794-70-1
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Appearance Solid
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분자량 428.98
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화학식 C21H25ClN6S
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Color White to off-white
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SMILES
C1(SN=C2N3CCN(CCCCN4N=NC5=C4C=CC=C5)CC3)=C2C=CC=C1.Cl
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선적
Room temperature in continental US; may vary elsewhere.
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보관
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
용액&용해도
In Vitro:
DMSO : 100 mg/mL (233.11 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (11.66 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (11.66 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (301 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
[1]. Tian JS, et al. Pharmacological effects of MT-1207 in bilateral renal artery stenosis hypertension and its hypotensive targets validation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024 Sep;178:117234. [Content Brief]
[2]. Wang P, et al. Discovery of MT-1207: A Novel, Potent Multitarget Inhibitor as a Promising Clinical Candidate for the Treatment of Hypertension. Journal of medicinal chemistry. 2024 Sep 26;67(18):16128-16144. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3311 mL | 11.6556 mL | 23.3111 mL | 58.2778 mL |
| 5 mM | 0.4662 mL | 2.3311 mL | 4.6622 mL | 11.6556 mL | |
| 10 mM | 0.2331 mL | 1.1656 mL | 2.3311 mL | 5.8278 mL | |
| 15 mM | 0.1554 mL | 0.7770 mL | 1.5541 mL | 3.8852 mL | |
| 20 mM | 0.1166 mL | 0.5828 mL | 1.1656 mL | 2.9139 mL | |
| 25 mM | 0.0932 mL | 0.4662 mL | 0.9324 mL | 2.3311 mL | |
| 30 mM | 0.0777 mL | 0.3885 mL | 0.7770 mL | 1.9426 mL | |
| 40 mM | 0.0583 mL | 0.2914 mL | 0.5828 mL | 1.4569 mL | |
| 50 mM | 0.0466 mL | 0.2331 mL | 0.4662 mL | 1.1656 mL | |
| 60 mM | 0.0389 mL | 0.1943 mL | 0.3885 mL | 0.9713 mL | |
| 80 mM | 0.0291 mL | 0.1457 mL | 0.2914 mL | 0.7285 mL | |
| 100 mM | 0.0233 mL | 0.1166 mL | 0.2331 mL | 0.5828 mL |
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